Serotonergic agents in the treatment of fibromyalgia syndrome

OBJECTIVE: To evaluate literature that discusses the treatment of fibromyalgia syndrome (FMS) with agents that involve the neurotransmitter serotonin. DATA SOURCES: Biomedical literature accessed through MEDLINE (1966-August 2001) and International Pharmaceutical Abstracts. DATA SYNTHESIS: The cause and pathophysiology of FMS remain elusive, although abnormalities in the serotonin pathway have been implicated. Several serotonergic agents have been studied for use in FMS. Trials and case reports focusing on the use of newer agents: the selective serotonin reuptake inhibitors, venlafaxine and tramadol, were reviewed. CONCLUSIONS: Current research suggests that the serotonergic agents may reduce at least some of the symptoms of FMS. However, medications that act on multiple neurotransmitters may prove to be more effective in symptom management. Additional long-term studies are required in order to validate these results.     

Suboptimal restraint affects the pattern of abdominal injuries in children involved in motor vehicle crashes

Background

Both solid and hollow visceral abdominal injuries have been associated with the use of seat belts in children involved in motor vehicle crashes. The relationship between the types of restraint used and the pattern of abdominal injury is unknown.

Methods

A probability sample of restrained children involved in crashes was enrolled in an ongoing crash surveillance system (1998 through 2002) linking insurance claims data to telephone survey and crash investigation data. Significant abdominal injuries were considered when the Abbreviated Injury Scale (AIS) score was ≥2 and were defined as hollow visceral (HV; intestine, bladder), or solid visceral (liver, spleen, pancreas, kidney). Restraint type was categorized as optimal restraint (OR) or suboptimal restraint (S-OR) based on the child’s age and size.

Results

For the 33 months of review, interviews were obtained for 13,558 restrained children aged 0 to 15 years, of which, 56% were OR (n = 7,591) and 44% were S-OR (n = 5,967). A significant abdominal injury was recorded in 78 children. A hollow visceral injury was recorded in 38 (9 OR and 29 S-OR), and a solid visceral injury in 32 (18 OR and 14 S-OR). Both hollow and solid visceral injuries were present in 8 children (2 OR and 6 S-OR). Suboptimally restrained children had a higher risk for hollow visceral injury when compared with optimally restrained children (Odds Ratio, 4.14 [95% Confidence Interval 1.33 to 13.22, P < .01]).

Conclusions

Among restrained children with intraabdominal injuries, those who were suboptimally restrained were 4 times more likely to have a hollow visceral than a solid visceral injury when compared with those who were optimally restrained. This suggests that the mechanism of injury for hollow viscus may be directly related to the improper positioning of the restraint.     

Transgenic and knockout mice to study the renin-angiotensin system and other interacting vasoactive pathways

Essential hypertension is an insidious disease in which the afflicted person risks disability and death from myocardial infarction and stroke. Many factors contribute to the development of essential hypertension, including environment, diet, daily stress, and genetics. Although several single gene disorders causing high blood pressure have been identified, the genetics of essential hypertension are much more complicated. The current hypothesis is that a combination of genetic variations in multiple genes may predispose a person to hypertension. Both overexpression and gene inactivation ("knockout") have proven useful tools to evaluate the genetics of essential hypertension and to identify pathways regulating blood pressure. Molecular and physiologic evaluations of transgenic and knockout mice carried out over the past 5 years have provided a plethora of information about the mechanisms of blood pressure regulation and the development and maintenance of hypertension. This review focuses on the newer mouse models that have been developed to investigate hypertension with an emphasis on vascular and renal mechanisms, contributed by the renin-angiotensin system, and other pathways intersecting with the renin-angiotensin system.     

Delta V as a predictor of significant injury for children involved in frontal motor vehicle crashes

OBJECTIVE: The objective of this study was to examine the association between delta V and risk of injury to children involved in frontal motor vehicle crashes. BACKGROUND: Previous studies, primarily focused on adult occupants, have demonstrated the relationship between crash severity, as measured by delta V and injury severity. As children have unique safety needs, these results cannot be directly applied to the pediatric population. METHODS: Case series crash investigation data and clinical injury information were reviewed from a child-focused crash surveillance system. Analyses were performed examining the relationship between the estimated delta V and any AIS > or = 2 or any AIS > or = 3 injury. RESULTS: Detailed crash investigation and clinical data were available on 407 children involved in 235 frontal crashes. The average delta V for all crashes was 29 +/- 16.9 kph [18 +/- 10.5 mph (range, 5-123 kph)]. Delta V was strongly and positively associated with the odds of both an AIS > or = 2 and AIS > or = 3 injury (P < 0.0001). The adjusted odds of at least one AIS > or = 2 injury increased on average by 56% (95% confidence interval [CI], 33%-85%) for each 10 kph increase in delta V. Similarly, the adjusted odds of at least one AIS > or = 3 injury increased on average by 67% (95% CI, 40%-102%) for each 10 kph increase in delta V. The delta V at which 50% of child occupants would be expected to sustain any AIS > or = 2 injury was 37 kph [23.0 mph (95% CI, 32-45 kph)], and any AIS > or = 3 injury was 63 kph [39.1 mph (95% CI, 51-infinity kph)]. CONCLUSION: Delta V is strongly predictive of injury risk for child occupants. As many newer generation cars are now fitted with event data recorders, this information is increasingly available and may become useful as a clinical predictor.     

Comparison of Remifentanil and Fentanyl in Patients Undergoing Craniotomy for Supratentorial Space-occupying Lesions

Background: Remifentanil hydrochloride is an ultra-short-acting, esterase-metabolized micro-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions.

Methods: Sixty-three adults gave written informed consent for this prospective, randomized, double-blind, multiple-center trial. Anesthesia was induced with thiopental, pancuronium, nitrous oxide/oxygen, and fentanyl (n = 32; 2 micro gram [center dot] kg [center dot] sup -1 min sup -1) or remifentanil (n = 31; 1 micro [center dot] kg sup -1 [center dot] min sup -1). After tracheal intubation, infusion rates were reduced to 0.03 micro gram [center dot] kg sup -1 [center dot] min sup -1 (fentanyl) or 0.2 micro gram [center dot] kg sup -1 [center dot] min sup -1 (remifentanil) and then adjusted to maintain anesthesia and stable hemodynamics. Isoflurane was given only after specified infusion rate increases had occurred. At the time of the first burr hole, intracranial pressure was measured in a subset of patients. At bone flap replacement either saline (fentanyl group) or remifentanil ([nearly equal] 0.2 micro gram [center dot] kg sup -1 [center dot] min sup -1) were infused until dressing completion. Hemodynamics and time to recovery were monitored for 60 min. Analgesic requirements and nausea and vomiting were observed for 24 h. Neurological examinations were performed before operation and on postoperative days 1 and 7.

Results: Induction hemodynamics were similar. Systolic blood pressure was greater in the patients receiving fentanyl after tracheal intubation (fentanyl = 127 +/- 18 mmHg; remifentanil = 113 +/- 18 mmHg; P = 0.004). Intracranial pressure (fentanyl = 14 +/- 13 mmHg; remifentanil = 13 +/- 10 mmHg) and cerebral perfusion pressure (fentanyl = 76 +/- 19 mmHg; remifentanil = 78 +/- 14 mmHg) were similar. Isoflurane use was greater in the patients who received fentanyl. Median time to tracheal extubation was similar (fentanyl = 4 min: range = -1 to 40 min; remifentanil = 5 min: range = 1 to 15 min). Seven patients receiving fentanyl and none receiving remifentanil required naloxone. Postoperative systolic blood pressure was greater (fentanyl = 134 +/- 16 mmHg; remifentanil = 147 +/- 15 mmHg; P = 0.001) and analgesics were required earlier in patients receiving remifentanil. Incidences of nausea and vomiting were similar.     

Executive function in first-episode schizophrenia: a three-year longitudinal study of an ecologically valid test

Executive function impairment is a key cognitive deficit in schizophrenia. However, traditional neuropsychological tests of executive function may not be sensitive enough to capture the everyday dysexecutive problems experienced by patients. Additionally, existing literature has been inconsistent about longitudinal changes of executive functions in schizophrenia. The present study focuses on examining the longitudinal change of executive functions in schizophrenia using the Modified Six Elements Test (MSET) that was developed based on the Supervisory Attentional System model and shown to be sensitive to everyday dysexecutive problems. In the present study, MSET performance was assessed in 31 medication-na?ve first-episode schizophrenic patients at four times over a period of three years, while the 31 normal controls were assessed once. Patients demonstrated impairment in MSET as compared to controls. Importantly, the MSET impairment persisted from the medication-na?ve state to clinical stabilization and the three years following the first psychotic episode though patients improved in a conventional executive test (Modified Wisconsin Card Sorting Test). Performance was not related to intelligence, educational level, symptom changes, age-of-onset, or duration of untreated psychosis. Better MSET performance at medication-na?ve state predicted improvement in negative and positive symptoms over the three-year period. These findings may suggest that MSET impairment is a primary deficit in schizophrenia that occurs early in the course of the illness and remains stable irrespective of clinical state for at least three years following the first episode of schizophrenia.     

In vivo bystander effect: cranial X-irradiation leads to elevated DNA damage, altered cellular proliferation and apoptosis, and increased p53 levels in shielded spleen

PURPOSE: It is well accepted that irradiated cells may "forward" genome instability to nonirradiated neighboring cells, giving rise to the "bystander effect" phenomenon. Although bystander effects were well studied by using cell cultures, data for somatic bystander effects in vivo are relatively scarce. METHODS AND MATERIALS: We set out to analyze the existence and molecular nature of bystander effects in a radiation target-organ spleen by using a mouse model. The animal's head was exposed to X-rays while the remainder of the body was completely protected by a medical-grade shield. Using immunohistochemistry, we addressed levels of DNA damage, cellular proliferation, apoptosis, and p53 protein in the spleen of control animals and completely exposed and head-exposed/body bystander animals. RESULTS: We found that localized head radiation exposure led to the induction of bystander effects in the lead-shielded distant spleen tissue. Namely, cranial irradiation led to increased levels of DNA damage and p53 expression and also altered levels of cellular proliferation and apoptosis in bystander spleen tissue. The observed bystander changes were not caused by radiation scattering and were observed in two different mouse strains; C57BL/6 and BALB/c. CONCLUSION: Our study proves that bystander effects occur in the distant somatic organs on localized exposures. Additional studies are required to characterize the nature of an enigmatic bystander signal and analyze the long-term persistence of these effects and possible contribution of radiation-induced bystander effects to secondary radiation carcinogenesis.     

Efflux studies allow further characterisation of the noradrenaline and 5hydroxytryptamine transporters in rat lungs

The aim of the present study was to further characterise the noradrenaline and 5hydroxytryptamine [5HT] transporters in rat lungs by examining the efflux of noradrenaline and 5HT, respectively. Lungs from rats were isolated and perfused via the pulmonary artery. After loading the tissue with ³H5HT or ³Hnoradrenaline the efflux of the relevant amine from the lungs was examined for 1525min. The rate constant for efflux of ³H5HT increased by 81% when Na⁺ ions were removed from the perfusion solution; increased gradually when a selective 5HT transporter inhibitor, 200nM citalopram, was added to the perfusion solution for the final 6min of efflux; and increased markedly and rapidly when substrates of the 5HT transporter, tryptamine (18μM) and 7methyltryptamine (12μM), were added for the final 6min of efflux. These effects of the substrates were abolished by 1μM citalopram, but were not significantly affected by 1μM desipramine, a selective uptake₁ inhibitor. On the other hand, the previously described substrateinduced increase in the rate of efflux of noradrenaline was significantly reduced by desipramine but was unaffected by citalopram. The results show that efflux of 5HT is mediated only by the 5HT transporter, with no significant contribution of uptake₁, and efflux of noradrenaline from rat lungs is mediated only by uptake₁ and not by the 5HT transporter. The effects of dopamine on the efflux of noradrenaline over a concentration range of 100-600nM were investigated and the results showed that 50% of the maximal increase in the rate of efflux occurred at a concentration of 275nM. This value did not differ from the K_m for uptake of dopamine. This result implies that the only factor affecting the substrate-induced increase in noradrenaline efflux is the affinity of the substrate for uptake₁. The efflux of noradrenaline was also examined in the absence and presence of two concentrations of desipramine (0.35and 1.5μM). Analysis of these results showed that uptake₁ contributed approximately 81% and diffusion 19% to the total efflux of noradrenaline and that 90% of the total noradrenaline efflux was subject to reuptake by uptake₁ into the pulmonary endothelial cells. Received: 23 January 1997 / Accepted: 26 March 1997     

Accuracy and sensitivity of finite element model-based deformable registration of the prostate

PURPOSE: Evaluate the accuracy and the sensitivity to contour variation and model size of a finite element model-based deformable registration algorithm for the prostate. METHODS AND MATERIALS: Two magnetic resonance images (MRIs) were obtained for 21 prostate patients with three implanted markers. A single observer contoured the prostate and markers and performed blinded recontouring of the first MRI. A biomechanical-model based deformable registration algorithm, MORFEUS, was applied to each dataset pair, deforming the second image (B) to the first image (A). The residual error was calculated by comparing the center of mass (COM) of the markers with the predicted COM. Sensitivity to contour variation was calculated by deforming B to the repeat contour of A (A2). The sensitivity to the model size was calculated by reducing the number of nodes (B', A', A2') and repeating the analysis. RESULTS: The average residual error of the registration for B to A and B to A2 was 0.22 cm (SD: 0.08 cm) and 0.24 cm (SD: 0.09 cm), respectively. The average residual error of the registration of B' to A' and B' to A2' was 0.22 cm (SD: 0.10 cm) and 0.25 cm (SD: 0.10 cm), respectively. The average time to run MORFEUS on the standard and reduced model was 3606 s (SD: 7788 s) and 56 s (SD: 16 s), respectively. CONCLUSIONS: The accuracy of the algorithm, equal to the image voxel size, is not affected by intraobserver contour variability or model size. Reducing the model size significantly increases algorithm efficiency.     

Correction to: Psoriasis in systemic lupus erythematosus: a single-center experience

Clinical Rheumatology - Prof. Ari Polachek on of the author of the published version of this article missed to add his second affiliation which is the Department of Rheumatology, Tel Aviv Sourasky...